The active domain of many proteins may in some cases be mimicked at least in part through the use of short peptide sequences derived from the active site of the protein (Massia and Hubbell, 1991, Yamada, 1991). Through this method, the activity of a specific protein can be conferred to an otherwise nonactive surface or matrix. This method allows a much higher concentration of active sequences to be immobilized onto a surface than is found naturally. While many peptides have been shown to have a monotonic correlation between density and cellular activity, other peptides are known to reach a maximum activity at a moderate level of peptide density. The best example is migration of cells on a surface coated with RGD (SEQ ID NO:2). If the concentration of RGD (SEQ ID NO:2) is too high, the surface binds too strongly to the cells, inhibiting cellular migration. However, if the RGD (SEQ ID NO:2) density is too low, then there is not enough traction for these cells to effectively migrate across the surface, leading to a maximal migration rate at a moderate surface concentration of peptide. (DiMilla, et al., 1991) Unfortunately, there is not very much research of the concentration dependent effect of these peptides in a three dimensional matrix. It is not possible to predict which peptides will show saturating behavior and it is not possible to predict at what peptide concentration maximal benefits will be observed.
While individual peptides can partially mimic the effect of the whole protein, the magnitude of this effect is typically lower. This is due to several reasons, including possible changes in conformation, peptide accessibility and changes in solubility between the peptide and the protein. One additional difference is that the interaction between cells and individual proteins or entire extracellular matrix involve simultaneously binding to multiple peptide sequences. (Martin, 1987, Kleinman, et al., 1993) Sometimes these sequences are on the same protein, but often they are on different proteins. In general it is not possible to predict which combinations might interact negatively, which might interact additively and which might interact synergistically.
Reports in the literature relate to findings that heparin-binding domains of proteins as well as receptor-mediated binding domains promote neuron adhesion and neurite extension. Many heparin binding domains have been identified (Table 1) and furthermore, haparin binding regions of several proteins such as neural cell adhesion molecule, fibronectin, laminin, midkine, and anti-thrombin III have been reported to promote neurite extension on two-dimensional surfaces. (Edgar, et al., 1984, Borrajo, et al., 1997, Kallapur and Akeson, 1992, Kaneda, et al., 1996, Rogers, et al., 1985) These heparin-binding domains have been reported by indirect evidence to interact with cell-surface proteoglycans by a number of methods including inhibition by soluble heparin, enzymatic removal of cell surface proteoglycans, and biochemical inhibition of proteoglycan synthesis (Kallapur and Akeson, 1992). These peptides have only been studies in 2-dimensional systems.